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Multiplexing Advances Redefine HTS

Multiplexing is a critical component of rapid screening technologies. At the annual meeting of the Society for Biomolecular Sciences held recently in Phoenix, a number of industry and academic scientists explained their pursuit of novel technologies that allow assays to be performed simultaneously on each well of a microtiter plate. Label-free technologies such as surface plasmon resonance (SPR) are available through various companies, and several contract research organizations are adept at their application.

Helena Nilshans, senior market director for life sciences at GE Healthcare, talked about the Biacore™ 4000 LMW extension package, which she reported “is mainly designed for small molecule drug discovery applications. Backed up by dedicated software tools for screening of fragments and other low molecular weight compounds, Biacore 4000 supports a range of assays from screening to characterization applications such as lead optimization.”

According to Olof Karlsson, Ph.D., a senior scientist in the Biacore R&D division, the amount of data generated on a conventional SPR system takes days to sort out with ordinary software. But with the Biacore 4000, less than two hours are required. “Not only the speed of the processing, but the overall quality of the data analysis is notably improved.”

Dr. Karlsson shared data detailing the multiplexing features of the Biacore 4000; he said that 16 targets can be run in parallel, processing up to 4,800 interactions in 24 hours. Both hardware and software are optimized for efficient large-scale assays, permitting 60 hours of unattended run time, he added. The system also includes an antibody-analysis package, allowing several interactions to be studied simultaneously.

Low molecular weight pharmaceuticals are far from an endangered species. “The vast majority of drugs are still small molecules, whose cost and convenience guarantee that they won’t soon be replaced by biologics. Biacore technology allows us to use information concerning specific structures, expanding the description from a small fragment into a model of a larger molecule, optimized for binding to its target.

“The software provides parameter analyses and identifies deviations. Elimination criteria start with the new data from a run and eliminate the bad data first, allowing us to promptly focus on the good candidates.”

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